This continuing education activity is supported through an unrestricted educational grant from Merck & Co, Inc.

Faculty

Murray Fingeret, OD, FAAO (Program Chair)
Chief of the Optometry Section
Brooklyn/St. Albans Campus
Department of Veterans Affairs New York Harbor Healthcare System
Clinical Professor
State University of New York College of Optometry.
New York, New York

Joseph Sowka, OD
Professor
Chief of Advanced Care Service
Director of Glaucoma Service
Nova Southeastern University College of Optometry
Fort Lauderdale-Davie, Florida

LEARNING METHOD AND MEDIUM

This educational activity consists of a case report and ten (10) study questions. The participant should, in order, read the Learning Objectives contained at the beginning of this activity, read the material, answer all questions in the post test, and complete the Activity Evaluation/Credit Request form. To receive credit for this activity, please follow the instructions provided below in the section titled To Obtain CE Credit. This educational activity should take a maximum of 1.0 hour to complete.

CONTENT SOURCE

ACTIVITY DESCRIPTION

There is a growing awareness of the impact of ocular surface disorders on the successful management of patients with ocular hypertension and glaucoma. Recent studies provide new insights into patient problems and concerns, and an increasing awareness of the significance of preservatives on ocular health. Improved versions of current therapies, and the availability of new therapies, provide opportunities for improved outcomes toward the prevention of glaucoma progression. Recently, a group of experts convened to discuss their insights and approaches for managing these patients. This CE activity brings you highlights from these case discussions in a 4-part series.

TARGET AUDIENCE

This educational activity is intended for optometrists.

Learning Objectives

Upon completion of this 4-Part CE Case Series, participants will be better able to:

Assess ocular surface health in patients on ocular antihypertensives

Review the evidence on the effects of preservatives on the ocular surface as they relate to ocular hypertension treatment regimens

Ian Benjamin Gaddie, OD, had a financial agreement or affiliation during the past year
with the following commercial interests in the form of Consultant: Alcon, Inc; Allergan,
Inc; Bausch + Lomb Incorporated; Marco Medical Management LLC; Merck & Co, Inc;
OCuSOFT; and Sucampo Pharmaceuticals, Inc.

Milton Hom, OD, had a financial agreement or affiliation during the past year with the
following commercial interests in the form of Consultant: Allergan, Inc; Bausch + Lomb
Incorporated; NicOx SA; and SARcode Bioscience, Inc; Contracted Research: Abbott
Medical Optics; Allergan, Inc; and Bausch + Lomb Incorporated.

Joseph Sowka, OD, had a financial agreement or affiliation during the past year with
the following commercial interests in the form of Consultant/Advisory Board: Alcon, Inc;
Merck & Co, Inc; and Sucampo Pharmaceuticals, Inc; Fees forpromotional, advertising
or non-CME services received directly from commercial interest or their Agents (eg,
Speakers Bureaus): Alcon, Inc; and Carl Zeiss Meditec, Inc.

DISCLOSURE ATTESTATION

Each of the contributing physicians listed above has attested to the following:

that the relationships/affiliations noted will not bias or otherwise influence his or her involvement in this activity;

that practice recommendations given relevant to the companies with whom he or she has relationships/affiliations will be supported by the best available evidence or, absent evidence, will be consistent with generally accepted medical practice; and

that all reasonable clinical alternatives will be discussed when making practice recommendations.

OFF-LABEL DISCUSSION

This activity includes off-label discussion of steroids for dry eye. Please consult products for all approved indications and administration.

GRANTOR STATEMENT

This CE activity is supported through an unrestricted educational grant from Merck & Co, Inc.

TO OBTAIN CE CREDIT

We offer instant certificate processing and support Green CE. Please take this post test and evaluation online by clicking the Take Exam button at the end of this case. Upon passing, you will receive your certificate immediately. You must answer 7 out of 10 questions correctly in order to pass, and may take the test up to 2 times. Upon registering and successfully completing the post test, your certificate will be made available online and you can print it or file it. Please make sure you take the online post test and evaluation on a device that has printing capabilities. There are no fees for participating in and receiving CE credit for this activity.

DISCLAIMER

The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of The State University of New York College of Optometry; MedEdicus LLC; Merck & Co, Inc; or Review of Optometry.

CASE PRESENTATION

Dr Fingeret: A 73-year-old African American male with a 7-year history of primary
open-angle glaucoma (POAG) presented for his quarterly glaucoma evaluation. He
complains of burning and stinging in each eye upon instillation of his ocular
antihypertensive medications. His aversion to the medications has worsened to the
point that he reports often neglecting to administer the medications. His ocular
antihypertensive regimen includes latanoprost (generic formulation) in each eye at
bedtime and timolol/dorzolamide (generic formulation) in each eye twice daily. The
patient also has been using over-the-counter artificial tears for several years. The
artificial tears no longer provide relief for his ocular discomfort.

PERTINENT EXAMINATION FINDINGS

External eye examination finds mild conjunctival hyperemia and pouting of the
meibomian glands with clear material expressed upon gentle pressure of the patient's
eyelids. A moderate amount of debris is visualized on his eyelashes. He also has some
corneal punctate staining. His tear break-up time is very fast. His current intraocular
pressures (IOPs), 25 mm Hg OD and 22 mm Hg OS, are 7 to 8 points higher than in
previous visits and are approaching pretreatment levels. The patient reports that he is
not using his ocular antihypertensive medications because of the irritation he
experiences when administering them, and he also states that his eyes feel irritated
constantly.

ASSESSMENT

This patient's POAG is complicated by ocular surface disease (OSD), which interferes
with his adherence to glaucoma therapies.

DISCUSSION

Dr Fingeret: What would be the other panelists' considerations for treating this
patient's glaucoma and OSD?

Dr Sowka: Before attempting to modify his ocular antihypertensives, I would embark
upon treating his meibomian gland dysfunction (MGD) and blepharitis. My
recommendation would be to apply profound lid hygiene: lid scrubs, hot compresses,
digital massage, and perhaps a course of oral doxycycline or topical azithromycin.
Getting his MGD treated first will likely improve his chances of tolerating any new ocular
antihypertensives.

Dr Fingeret: Would you consider the use of topical steroids on his eyelids?

Dr Sowka: I would consider topical steroids only for severe dry eye. Using a
steroid is always risky because it can cause an IOP spike—an added risk here because
this patient has not been using his glaucoma therapies.

If this option is pursued, however, because of extremely severe OSD and uncomfortable
dry eye, I would use only a small dose for a short period of time. I recently have done
this with a patient of mine. Loteprednol, 0.2%, (brand formulation) was too expensive,
so I prescribed the generic fluorometholone. Both steroids have a low propensity to elevate IOP.1,2 In my patient's case, a week of steroid treatment was life changing and
so far, no IOP rise, thankfully. Applying a steroid topically to this case patient's eyelid
rather than instilling a steroid directly into his eye may minimize the risk of steroid-induced IOP increases.

Dr Fingeret: Dr Sowka, are you suggesting discontinuing all his glaucoma
medications—so long as the patient does not have advanced glaucoma—and treating
the eyelids and the ocular surface until the MGD and blepharitis resolve?

Dr Sowka: Yes, with an additional caveat: If this patient had a pretreatment IOP above
40 mm Hg, I would not discontinue his glaucoma medications. Another option is to
reduce the glaucoma medications down to 1 agent and to proceed on the course of
blepharitis treatment.

Dr Hom: I would take a diagnostic approach initially, investigating for Demodex mite
infestation. There are several reasons to first rule out Demodex as the cause of his
ocular signs and symptoms. Firstly, in patients who are aged 70 years and older, the
prevalence of Demodex approaches 100%,3 and this patient is 73 years old, placing him
in the high-risk age group. Secondly, consider that Demodex might be a cause of the
patient's blepharitis4 and worsening MGD.5,6 A 2011 study conducted in the Philippines
showed that 85% of patients with MGD had underlying Demodex infestation.7 Thirdly,
the images of the patient's eyes indicate some lid debris at the base of the eyelashes. (Figure 2) That debris could be cylindrical dandruff, although it is difficult to visualize
against the patient's dark skin. In a 2005 study, Gao and colleagues found that
cylindrical dandruff is 80% pathognomonic for Demodex.4(Figure 7) Lid debris typically
appears farther down the lash, but in Demodex infestation, a more typical presentation
of lid debris appears at the eyelash base.4 This cylindrical debris is caused either by Demodex folliculorum mites that live in the follicle and/or by Demodex brevis mites that
live deep in the eyelash's sebaceous glands and in the meibomian gland.4 The lid debris
is the waste products that the mites leak out from the follicle.

To check for the presence of the parasites, epilate the lash and look at the eyelash
underneath a light microscope to see if there are any mites visible. The presence of the Demodex mites could explain the patient's discomfort. And if Demodex is indeed the
cause of discomfort, my suggestion is to treat the patient with in-office tea tree oil
treatments.5 Clinicians should be aware that Demodex might be the culprit in many lid
disease cases that are resistant to routine therapies. If a patient is not getting better with
routine treatment, Demodex could be the reason.

An important point with respect to Demodex treatment is that Demodex infestation is
usually related to rosacea.3,8 Treatment for acne rosacea usually involves steroid
therapy. However, steroids should be avoided in patients with Demodex because
steroids may increase mite counts.9 Thus, treatment of the rosacea with steroids
actually could cause the Demodex infestation to worsen.10 Optometrists are often reluctant to use steroids in a patient with glaucoma in the first
place because of its effect on IOP. Thus, if this patient has Demodex infestation, I would
not use steroids on the patient's eyelids.

Dr Gaddie: I agree completely with Dr Hom that this appears to be a case complicated
by Demodex. While the prevalence is close to 100% at this age3, not everyone with Demodex has symptoms or requires treatment.6 But certainly in this case the condition
does warrant treatment, and I think you could do so without stopping glaucoma therapy.
I also use a tea tree oil treatment for Demodex and doing so does not necessitate discontinuation of glaucoma treatment. In my clinical experience I have found that
patients who are on prostaglandin analogs are more susceptible to Demodex, possibly
as a result of the inflammatory mechanisms of the drugs.

Certainly laser trabeculoplasty would be a great option to otherwise reduce the load of
topical medications and their associated preservatives vs a preservative-free medication
option.

Dr Fingeret: Allow me to relate how I managed this patient's glaucoma in light of his
OSD. I treated his OSD condition with warm compresses, meibomian gland
expression, and eyelid cleaning. I added omega-3 fatty acid therapy11,12,13 and switched
him to preservative-free ocular antihypertensives: tafluprost (brand formulation) and the
combination preservative-free dorzolamide/timolol (brand formulation). When the patient
returned a month later, he felt better. His eyes looked relatively white, and he reported
that the ocular antihypertensive medications were not causing stinging in his eyes. His
IOPs were 13 mm Hg OD and 14 mm Hg OS, which confirmed that his previously poorly
controlled IOP was related to poor adherence to glaucoma therapy.

The question then arises: Were the patient's OSD symptoms independent of his ocular
antihypertensive medications, or did the medications contribute to the OSD? My
assessment was the latter. Although his medications may not have been the instigators
of or culprits in the OSD, they were at least contributing to it. Consequently, switching to
a preservative-free ocular antihypertensive eliminated any contribution of the
benzalkonium chloride (BAK)-preserved ocular antihypertensives aggravating the
patient's OSD.

When corneal staining and hyperemia are present with an unclear cause, my
assessment is that BAK may be exacerbating OSD. In a 2008 study examining the
prevalence of OSD in patients with glaucoma, Leung and colleagues found that 59% of
patients reported symptoms of OSD.12 The researchers also investigated the link
between the number of BAK-containing drops and clinical test results for OSD. After
controlling for age and sex, each additional BAK-containing drop was associated with
approximately twice the risk of abnormal results on corneal and conjunctival lissamine
green staining (odds ratio = 2.03; 95% confidence interval = 1.06 – 3.89; P=.034).14 BAK
has been found to exacerbate conditions that are deleterious to the ocular surface,
including blepharitis, MGD, tear film instability, conjunctival inflammation, and keratitis.15 Compared with preservative-free ocular antihypertensives, preserved ocular
antihypertensives, particularly those containing BAK, can aggravate dry eye disease
and can cause a markedly increased prevalence and frequency of symptoms of
burning, stinging, and discomfort.15 Even if there had been preexisting OSD prior to BAK
exposure in this case patient, my thought was that a preservative-free ocular antihypertensive would avoid additional insult to the eye and might make the patient's
eyes feel better.

Dr Sowka: Based on the success of Dr Fingeret's treatment plan, the patient's
condition was unlikely to have been caused by Demodex infestation. Nonetheless,
optometrists should consider adding Demodex to the differential diagnosis in a patient
presenting with some of the following signs and symptoms: blepharitis, MGD, OSD,
debris near the eyelash base. Also, a Demodex treatment plan is a helpful addition to
the optometrist's armamentarium. Regardless of why the treatment for this patient was
a success, whether it was due to the blepharitis treatment or to the switch to a
preservative-free ocular antihypertensive, the end result was a positive outcome—a
patient with glaucoma who is now comfortable using his ocular antihypertensive
medications.